مواضيع المحاضرة: Mineral metabolism
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Mineral metabolism

Minerals: Are essential for normal growth and maintenance of body.
Major elements: Requirement ˃ 100 mg/day
1- Calcium
2-Magnesium
3- Phosphorus
4- Sodium
5- Potassium
6- Chloride
7- Fluoride
Trace elements: Requirement ˂ 100 mg/day
1- Iron
2- Iodine
3- Copper
4- Manganese
5- Zinc
6- Molybdenum
7- Selenium
Some are necessary for the body but their exact functions are not known.
Ex: Chromium. Nickel, Bromide, Lithium, Barium.
Non – Essentials: seen in tissues. Contaminants in food stuffs.
Ex: Rubedium, Silver, Gold, Bismuth.
Toxic: should be avoided.
Ex: Aluminium, Lead, Cadmium, Mercury.
1- Calcium:
a-Participates in the structure of bones and teeth. At least 99% of the total amount of calcium is in the bones and teeth. Calcium in the bones is transformed into a hydroxyapatite - Ca10(PO4)6(OH)2 but the bones also contain significant amounts of calcium phosphate, carbonate, citrate, fluoride, magnesium, strontium, trace and minor amounts of other salts. Minerals account about 50% of the total bone mass. The rest is organic matrix in which are proteins, glycoproteins and proteoglycans that bind calcium salts.
b- Metabolic regulation. This is one of the main roles of calcium. Protein kinases, which modulate the activity of key enzymes as a response to hormone binding to the surface of cells, are calcium activated - either directly, or binding to a protein that binds calcium – calmodulin.
c- Regulation of cellular activity. These include nerve and muscle function, hormone action, blood coagulation, cell motility, and many others. Regulates muscle contraction by regulating the contractility of actin and myosin. Since it participate in such a large number of cellular regulation it is also called the second messenger.
d- Intermediates in the reaction of cells to various stimuli. The way of this action is analogous to the regulatory actions of cyclic nucleotides. Effects of calcium is mediated by an intracellular receptor protein - calmodulin, which binds calcium ions when their concentration in the reaction to the stimulus increases.
e- It is the part of many metalloenzyme. For example. α-amylase and phospholipase contain calcium as an essential part of the catalytic. Osteocalcin is a protein from the bones which is important for normal bone mineral crystallization. Calbindin D is essential for intestinal absorption of calcium, the translation of calcium into the cells and the absorption of calcium from the glomerular filtrate in the kidney. Some of the blood proteins must bind calcium for their activity. Many anticoagulants bind calcium chelate structures (such as EDTA and citrate).
In the calcium-binding proteins calcium effect on:
1- Secretion of hormones and neurotransmitters. On this case it initiate cellular secretory vesicles to fuse with the surface of membrane and then exocytosis.
2- Cell adhesion. Kaderine are calcium-dependent proteins that regulate cell adhesion and normal contact inhibition of cell replication. Defect in the function of kaderine is linked to the development of malignancy.
3- Cytoskeleton proteins.
The importance of Ca2+ in these activities is reflected in the precision which regulates the concentration of Ca2+concentrations.
● Normal plasma contains 9-11 mg of calcium per 100 mL.
Calcium Deficiency: There are Two Types of Calcium Deficiency
a- Dietary calcium deficiency: exists in individuals who are not getting enough calcium intake through their daily nutrition or supplement intake. What happens here is that the natural calcium storage within the bones becomes depleted. As a result, the bones begin to weaken and thin at an alarming rate. This deficiency can also lead to osteoporosis, a disease of the bones that triggers bone degeneration, a ‘humped’ back, a major increased risk of fractures, and other serious concerns.
b- hypocalcemia: has to do with low levels of calcium within the blood. Whereas dietary calcium deficiency is a result of inadequate nutritional intake, hypocalcemia is usually caused by certain medications or even medical conditions like hypoparathyroidism. Hypocalcemia is particularly concerning as the body will readily pull calcium from the bones in the event of a blood calcium deficiency in orders to support the proper function of the brain, heart, nerves, and muscles.
2- Magnesium: Magnesium is a cofactor in over 300 enzymatic reactions, particularly those involved in the metabolism of food components and the creation of new molecules important for human health.
1-For all enzymatic reactions that require energy stored in molecules of adenosine triphosphate (ATP) is required magnesium.
2- The synthesis of various molecules. Such molecules include proteins, nucleic acids, nucleotides, fatty acids and carbohydrates.
3- Activation of muscle concentration. Magnesium interacts with calcium in many body processes, such as regulation of blood vessels, contraction of muscles - including the heart muscle. Calcium stimulates contraction of muscles and blood vessels, while magnesium relaxes muscles and dilates blood vessels.
4- Detoxification.
5- The bone structure.
6- Ionic transport. Magnesium is involved in the maintenance of membrane electrical potential and the transport of sodium, potassium and calcium across the plasma membrane. Magnesium is involved in the transmission of nerve impulses.
7- Hormonal activity. Magnesium is necessary for the action of compounds that play a key role in the transfer of information from the hormones and other stimuli that cause chemical reactions within the cell. Magnesium increases the excretion of hormone insulin and contributes to a better entry into the cell. In this way, magnesium participates in the metabolism of carbohydrates.
Normal magnesium levels are between 1.7–2.2 mg/dL with levels less than 1.7 mg/dL (0.7 mmol/L) defining hypomagnesemia.
Hypomagnesemia: also spelled hypomagnesaemia, is an electrolyte disturbance in which there is a low level of magnesium in the blood. Symptoms include tremor, nystagmus, seizures, and cardiac arrest including torsade de pointes. Causes include alcoholism, starvation, diarrhea, increased urinary loss, and poor absorption from the intestines. Hypomagnesemia is not necessarily magnesium deficiency. Hypomagnesemia can be present without magnesium deficiency and vice versa. Specific electrocardiogram (ECG) changes may be seen.


3- Phosphorus : The roles of phosphorus in the human body:
1- Building bones and teeth,
2- Use of carbohydrates (sugar) and fat,
Protein synthesis, 3-
Growth, maintenance and healing of cells and tissues, 4-
5- Serves as a source of energy (in the molecule adenosine triphosphate - ATP and creatine phosphate),
Muscle contractions, 6-
7- Kidney function,
Regulation of heart rate, 8-
9- Transmission of nerve impulses,
Reduces muscle soreness after hard work, 10-
Production of genetic material (DNA, RNA), 11-
12- Maintains balance and helps in the utilization of other vitamins and minerals (vitamins of the B group, vitamin D, iodine, magnesium, zinc),
Part of the cell membrane (within the phospholipid), 13-
14- Necessary in all the metabolic pathways in the body (energy production, cell division, ….etc),
15- A part of many enzymes and hormones,
16- Maintain normal acido-base balance in the body (pH).
Hypophosphatemia A low level of blood phosphate is defined as a level below 0.8 mmol/L, is an electrolyte disturbance in which there is an abnormally low level of phosphate in the blood. The condition has many causes, but is most commonly seen when malnourished patients (especially chronic alcoholics) are given large amounts of carbohydrates, which creates a high phosphorus demand by cells, removing phosphate from the blood (refeeding syndrome). homeostasis in terms of bone content of phosphate and renal excretion is controlled by vitamin D, parathyroid hormone (PTH), and fibroblast growth factor 23(FGF 23).
Normal range is about 0.8 to 1.4 mmol/L in adults and slightly higher in children.
Significant hypophosphataemia (below 0.4 mmol/L) may occur due to redistribution into cells, renal losses or decreased intake. Patients with low phosphate often also have other electrolyte deficiencies.
Sodium: 4-
sodium is the principal cation in the extracellular fluid and its main functions are regulation of blood volume, blood pressure, osmotic balance and maintain a constant pH. it is also essential for acid-base balance and nerve conduction. More than 95% of ingested salt is absorbed by the gut and, as part of the electrolyte regulatory system, urinary sodium losses increase when the body has surplus sodium. Often, the main excretion of sodium is by sweat.
Renin–angiotensin system - hormone system that regulates blood pressure and fluid balance influences the amount of sodium in the body. Lowering blood pressure, and serum sodium in the kidneys leads to the formation of renin. Renin is an enzyme that is known as angiotensin-converting-enzyme and mediates the regulation of extra cellular fluid volume (plasma, lymph, intestinal fluid), and arterial vasoconstriction. In this way, regulate blood pressure. Renin causes the production of aldosterone and angiotensin (hormones) that cause sodium excretion in the urine. Increasing the concentration of sodium decreases renin formation and sodium returns to normal. Sodium is also essential for the functioning of neurons and osmoregulation between cells and the extracellular fluid. In humans, this process is regulated by the Na+/K+ pump.
Briefly, an increase in plasma osmolality occurs when the plasma becomes more concentrated; this can be produced either by dehydration or by excessive salt intake, producing stimulation of osmoreceptors and the sensation of thirst. When the thirst centre in the hypothalamus is stimulated, more water is taken into the intestine and subsequently enters the bloodstream. Simultaneously, endocrine systems stimulate the kidneys to retain more salt and water.
During prolonged exercise or hot weather, blood flow through the skin is adjusted and water and salt may be lost from the body through sweating in order to cool the body down and to maintain deep body temperature.
There are some pathological conditions that could cause hyponatraemia (sodium concentration in the serum that is lower than normal). However, depletion of body sodium in healthy individuals is very unlikely, because people tend to eat excessive amounts of sodium, beyond their physiological needs.
The reference range for serum sodium is 135-145 mmol/L.
5- Potassium:
Potassium regulates water and salt metabolism in the cell, osmotic pressure, acid-base balance, normalizes heartbeat, participate in the surrender of nerve impulses muscles, increases removal of sodium and water from the body and activates certain enzymes. In addition, potassium plays an important role in protein biosynthesis and the conversion of blood sugar into glycogen. Activates a number of enzymes, especially those involved in energy production. Stimulates normal intestinal movements. Potassium is the most important ion inside the cells. There is almost as much potassium inside the cell as there is sodium in the body fluids. the most important function of potassium is in the physiology of the muscles.
A low potassium level has many causes but usually results from vomiting, diarrhea, adrenal gland disorders, or use of diuretics.
1- A low potassium level can make muscles feel weak, cramp, twitch, or even become paralyzed, and abnormal heart rhythms may develop.
2- The diagnosis is based on blood tests to measure the potassium level.
3- Usually, eating foods rich in potassium or taking potassium supplements by mouth is all that is needed.
Reference Range:
Potassium is an electrolyte, which is a mineral in the blood that can be measured by a blood test. Potassium is ingested through food and electrolyte-enhanced beverages and excreted primarily through urine.
The reference ranges of serum/plasma potassium levels are as follows:
Adults: 3.5-5.1 mEq/L or mmol/L
Results can be affected by infusion of potassium-containing fluids or an infusion of glucose or insulin.
6- Chloride: is the most abundant free anion in animal cells, and performs or determines fundamental biological functions in all tissues.
Chloride channels are integral membrane proteins that regulate the movement of chloride ions across cellular membranes. They perform a vital role in physiological processes such as cell volume regulation, epithelial transport, the regulation of nerve and muscle cell membrane excitability and in determining the pH within cytoplasmic membrane-bound organelles. Several genetic diseases are caused by mutations within chloride channel genes. Chloride ion (Cl-) is the major anion in the extracellular fluid.
Main function:
1- regulate water balance (osmotic pressure and acid base) as it is the part of NaCl.
2- nerve impulse conduction
3- hydrochloric acid formation in stomach
4- plasma level of chloride change might cause abnormal metabolism of Na+ &
Cl- that might lead to:-
a- hyperchloraemia
b- hypochloremia
hypochloremia is an electrolyte disturbance in which there is an abnormally low level of the chloride ion in the blood.
The normal serum range for chloride is 97 to 107 mEq/L.


7- Flouride: Fluoride is an inorganic, monatomic anion of fluorine with the chemical formula F. Fluoride reduces the incidence of tooth decay and helps maintain bone structure. Though fluoride is mostly obtained from fluoridated water, it is also found in seafood, gelatin and tea. Fluoride is the simplest anion of fluorine. Its salts and minerals are important chemical reagents and industrial chemicals, mainly used in the production of hydrogen fluoride for fluorocarbons. In terms of charge and size, the fluoride ion resembles the hydroxide ion. Fluoride ions occur on earth in several minerals, particularly fluorite, but are only present in trace quantities in water. Fluoride contributes a distinctive bitter taste. It contributes no color to fluoride salts. Fluoride helps strengthen tooth enamel. Protects teeth from damage by creating compounds with calcium and phosphorus, which are stronger and less soluble than other calcium salts. These compounds remain in the bones and are hardly absorbed into the circulation in case of need for calcium. Children whose mothers during pregnancy consume enough fluoride have less damage to the teeth than children whose mothers had not consumed enough of this nutrient. Bones are more stable and resistant to degradation if the food has a sufficient amount of fluoride. Fluoride has been described as an essential element needed for normal development and growth of animals and extremely useful for human beings. Fluoride is abundant in the environment and the main source of fluoride to humans is drinking water. It has been proved to be beneficial in recommended doses, and at the same time its toxicity at higher levels has also been well established. Fluoride gets accumulated in hard tissues of the body and has been know to play an important role in mineralization of bone and teeth. At high levels it has been known to cause dental and skeletal fluorosis. There are suggested effects of very high levels of fluoride on various body organs and genetic material. The purpose of this paper is to review the various aspects of fluoride and its importance in human life.

Fluoride or fluorine deficiency is a disorder which may cause increased dental caries (or tooth decay, is the breakdown of dental tissues by the acidic products released by the "bacterial fermentation of dietary carbohydrates.") and possibly osteoporosis (a bone disorder which leads to a decrease in bone mass, and an increase in bone fragility), due to a lack of fluoride in the diethowever, there are anti-osteoporotic functional food ingredients that can help decrease the risk of osteoporosis fractures. In terms of dietary sources, fish and tea are considered natural sources of fluoride, as well as tap water that has been fluoridated. The extent to which the condition truly exists, and its relationship to fluoride poisoning has given rise to some controversy. Fluorine is not considered to be an essential nutrient, but the importance of fluorides for preventing tooth decay is well-recognized, although the effect is predominantly topical. Prior to 1981, the effect of fluorides was thought to be largely systemic and preeruptive, requiring ingestion. Fluoride is considered essential in the development and maintenance of teeth by the American Dental Hygienists' Association. Fluoride is also essential as it incorporates into the teeth to form and harden teeth enamels so that the teeth are more acid resistant as well as more resistant to cavity forming bacteria. Caries-inhibiting effects of fluoride were first seen in 1902 when fluoride in high concentrations was found to stain teeth and prevent tooth decay. Fluoride salts, particularly sodium fluoride (NaF), are used in the treatment and prevention of osteoporosis. Symptoms such as fractured hips in the elderly or brittle and weak bones are caused due to fluorine deficiency in the body. Fluoride stimulates bone formation and increases bone density, however bone with excess fluoride content has an abnormal structure resulting in increased fragility. Thus fluoride therapy results in large increases in bone mineral density but the effect on fracture rates, while positive, is small. Disputes over the essentiality of fluorine date back to the 19th century, when fluorine was observed in teeth and bones. In 1973 a trial found reduced reproduction in mice fed fluorine-deficient diets, but a subsequent investigation determined that this was due to reduced iron absorption. Fluoride reduces the incidence of tooth decay and helps maintain bone structure. Though fluoride is mostly obtained from fluoridated water, it is also found in seafood, gelatin and tea.
Normal reference range 0.3 - 2.2 µmol/l.
On fluoride treatment 3.3 - 13.7 µmol/l.
Iron:
Iron is a chemical element with symbol Fe and atomic number 26. It is the fourth most common element in the Earth's crust. Iron exists in a wide range of oxidation states, +2 to +6, although +2 and +3 are the most common. Iron plays an important role in biology, forming complexes with molecular oxygen in hemoglobin and myoglobin; these two compounds are common oxygen transport proteins in vertebrates. Iron is also the metal at the active site of many important redox enzymes dealing with cellular respiration and oxidation and reduction in plants and animals. A human male of average height has about 4 grams of iron in his body, a female about 3.5 grams. This iron is distributed throughout the body in hemoglobin, tissues, muscles, bone marrow, blood proteins, enzymes, ferritin, hemosiderin, and transport in plasma. Iron is a mineral that the body needs for many functions. For example, iron is part of hemoglobin, a protein which carries oxygen from the lung throughout our body. It helps the muscles store and use oxygen. Iron is also part of many other proteins and enzymes. The body needs the right amount of iron. If it has too little iron, it may develop iron deficiency anemia. Causes of low iron levels include blood loss, poor diet, or an inability to absorb enough iron from foods. People at higher risk of having too little iron are young children and women who are pregnant or have periods. Too much iron can damage your body. Taking too many iron supplements can cause iron poisoning. Some people have an inherited disease called hemochromatosis. It causes too much iron to build up in the body.
Normal value range:
Iron: 60 to 170 micrograms per deciliter (mcg/dL) or 10.74 to 30.43 micromoles per liter (micromol/L).
Total iron binding capacity (TIBC): 240 to 450 mcg/dL or 42.96 to 80.55 micromol/L
Transferrin saturation: 20% to 50% (transferrin moves iron through the blood).
Lower-than-normal levels may mean:
Long-term digestive tract bleeding
Heavy menstrual bleeding
Intestinal conditions that cause poor absorption of iron
Not enough iron in the diet
Pregnancy
Copper:
1- Copper is a chemical element with symbol Cu.
2- Copper is an important component of many enzymes in the body and play an important role in cell energy production. Activity of these enzymes is highest in the heart, brain, liver and kidney.
3- In addition, enzymes that are responsible for connective tissue proteins formation (collagen and elastin) require copper.
4- Copper is necessary for the development and maintenance of blood vessels, skin, bones and joints. It helps in preserving cells of the nervous system. Also has a beneficial effect on osteoporosis (brittle bone disease due to lack of calcium).
5- Copper is involved in the release of iron from their depot, the creation of bone marrow and maturation of red blood cells.
6- Copper is essential for the synthesis of phospholipids of cell membranes and thus maintain myelin that separates the nerve cell from the environment and regulates the levels of the neurotransmitters.
7- Copper is a component of the enzyme copper-zinc superoxide dismutase (Cu / Zn SOD), which serves as an antioxidant essential to preserve the body from damage caused by free radicals.
8- Copper is very important in creating the immune response to infection.
9- Copper is also necessary for the maturation and function of T cells. It also plays an important role in the contraction of the heart muscle, as well as in the healthy functioning of small blood vessels that control blood flow, nutrients and waste products.
10- Copper deficiency can manifest in parallel with vitamin B12 and other nutritional deficiencies. The most common cause of copper deficiency is a remote gastrointestinal surgery, such as gastric bypass surgery, due to malabsorption of copper, or zinc toxicity.
11- Menkes disease is a genetic disorder of copper deficiency involving a wide variety of symptoms that is often fatal. The deficiency in copper can cause many hematological manifestations, such as myelodysplasia, anemia, leukopenia (low white blood cell count) and neutropenia (low count of neutrophils, a type of white blood cell that is often called "the first line of defense" for the immune system).
12- Copper testing is primarily used to help diagnose Wilson disease, a rare inherited disorder that can lead to excess storage of copper in the liver, brain, and other organs. Less commonly, a copper test may be used to detect copper excess due to another condition, to detect a copper deficiency, or to monitor treatment for one of these conditions. Copper is an essential mineral but in excess, it can be toxic. In the blood, most of it is incorporated into the enzyme ceruloplasmin and only a small amount is in a "free" or unbound state. Typically, a total blood copper test is ordered along with a ceruloplasmin level.
Zinc Toxicity
Increased consumption of zinc is another cause of copper deficiency. Zinc is often used for the prevention or treatment of common colds and sinusitis (inflammation of sinuses due to an infection), ulcers, sickle cell disease, celiac disease, memory impairment and acne. Zinc is found in many common vitamin supplements and is also found in denture creams. Recently, several cases of copper deficiency myeloneuropathy were found to be caused by prolonged use of denture creams containing high quantities of zinc. Metallic zinc is the core of all United States currency coins, including copper coated pennies. People who ingest massive amount of coins will have elevated zinc levels, leading to zinc toxicity induced copper deficiency and thus displaying neurological symptoms. This was the case for a 57-year-old woman diagnosed with schizophrenia. The woman consumed over 600 coins, and started to show neurological symptoms such as unsteady gait and mild ataxia.
Iodine
Iodine is a component of the thyroid hormones thyroxine and triiodothyronine that determine the rate of metabolism in the body. This refers to the conversion of food into energy in the body, and also how to use that energy. Thyroid hormones are essential for the growth and development of organs, particularly the brain, reproductive system, nervous system, bones, skin, hair, nails and teeth. The thyroid gland is involved in the production of proteins, cholesterol synthesis, carbohydrate absorption and the conversion of carotene to vitamin A. Thyroxine is important for the regulation of body weight.
Iodine Deficiency
Iodine is an element that is needed for the production of thyroid hormone. The body does not make iodine, so it is an essential part of your diet. Iodine is found in various foods. If you do not have enough iodine in your body, you cannot make enough thyroid hormone. Thus, iodine deficiency can lead to enlargement of the thyroid (goiter) hypothyroidism and to mental retardation in infants and children whose mothers were iodine deficient during pregnancy.


Mineral metabolism





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